BIODEMOGRAPHY OF AGING: INSIGHTS FROM TWINS AND THE OLDEST-OLD IN DENMARK

Abstract The Danish Twin Registry holds health information from surveys and registers on more than 180,000 twins born in Denmark since 1870. Life course studies of the oldest twin cohorts show moderate heritability of lifespan but a substantial genetic influence on physical and cognitive functioning throughout life, i.e., twins are growing old but not growing apart, in terms of health phenotypes. Twins experience substantial growth restriction in the last intrauterine trimester. The generalizability of aging studies of twins hinges on whether this early life exposure has long-lasting health consequences. Generally, after the infant period, twin-singleton health differences are small, and during the 20th century, they have vanished. In the older twin cohorts, sex differences in the association between number of offspring and oral health late in life provided support for the proverb known in many countries: “A tooth per child”. Twin studies of biomarkers of aging revealed that perceived age estimated by lay assessors based on photos is a strong biomarker of aging. The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies of the oldest old were established to study secular trends in the health and functioning of the very old. Among the main findings of the studies are: Exceptional longevity does not lead to exceptional levels of disability; summed over cohorts, more people are living to the highest ages and are functioning better – and this progress is seen across the spectrum of health and functioning – offering hope for continued progress in health and survival among the oldest in society.

James W. Vaupel, PhD (1945-2022), was an international leader in demography and aging research and a pioneer in the field of biodemography.He was a highly creative researcher and very entrepreneurial in the development of new interdisciplinary research environments.This symposium highlights a few of the biodemographic research areas that Dr. Vaupel has been a catalyst for.Denmark was Dr. Vaupel's home country during the last third of his life, and Dr. Christensen reports on findings from Danish nationwide genetic-epidemiological studies on twins and the oldest old: familial influence on aging phenotypes, cohort differences in health among the oldest old, associations of early life events with late life health, as well as tongue-in-cheek research on perceived age and teeth.Dr. Alberts discusses the 'invariant rate of aging' hypothesis that was developed by Vaupel and others.She presents comparative analyses from multiple nonhuman primate populations showing that, while life expectancy can continue to improve, we probably can't slow the demographic rate of aging.Dr. Campos presents evidence from a wild baboon population in Kenya that glucocorticoid levels-biological markers of stress responses-are strong prognostic indicators of survival and may be key explanations of life span disparities.Dr. Carey presents key discoveries from large-scale studies involving the Mediterranean fruit fly.These include the slowing of mortality at older ages, context-specific sex mortality differentials, a behavioral biomarker for morbidity, dietary conditions for maximizing lifespan versus reproduction and a stationary population identity whereby life lived equals life left.The Danish Twin Registry holds health information from surveys and registers on more than 180,000 twins born in Denmark since 1870.Life course studies of the oldest twin cohorts show moderate heritability of lifespan but a substantial genetic influence on physical and cognitive functioning throughout life, i.e., twins are growing old but not growing apart, in terms of health phenotypes.Twins experience substantial growth restriction in the last intrauterine trimester.The generalizability of aging studies of twins hinges on whether this early life exposure has long-lasting health consequences.Generally, after the infant period, twin-singleton health differences are small, and during the 20th century, they have vanished.In the older twin cohorts, sex differences in the association between number of offspring and oral health late in life provided support for the proverb known in many countries: "A tooth per child".Twin studies of biomarkers of aging revealed that perceived age estimated by lay assessors based on photos is a strong biomarker of aging.The 1895The , 1905The , 1910The and 1915 Danish Birth Cohort Studies of the oldest old were established to study secular trends in the health and functioning of the very old.Among the main findings of the studies are: Exceptional longevity does not lead to exceptional levels of disability; summed over cohorts, more people are living to the highest ages and are functioning better -and this progress is seen across the spectrum of health and functioning -offering hope for continued progress in health and survival among the oldest in society.

THE LONG LIVES OF PRIMATES AND THE 'INVARIANT RATE OF AGING' HYPOTHESIS Susan Alberts, Duke University, Durham, North Carolina, United States
Can we slow the rate of human aging?A decades-long trend toward increasing life expectancy and greater lifespan equality in human populations raises the possibility that we can.But the rate of aging is closely correlated with other traits and may be highly constrained or even relatively fixed within species, according to the 'invariant rate of aging' hypothesis.To gain insight into biological constraints on aging, we use an unprecedented collection of datasets from 39 human and nonhuman primate populations, representing 7 genera distributed across the order Primates.We show that the highly regular linear relationship between life expectancy and lifespan equality reported in humans is recapitulated in other primate genera, and that variation in the rate of aging is several orders of magnitude smaller than pre-adult and age-independent mortality, which are highly variable within genera.Thus, within primate genera, longer life expectancies are associated with fewer early deaths, but not with a lower rate of aging.We also demonstrate that changes in the rate of aging, but not other ageing parameters, can produce striking, species-atypical changes in mortality patterns.Our results support the invariant rate of aging hypothesis, suggesting biological constraints on how much we can slow the human rate of aging.Abstract citation ID: igad104.0198

STRESS AND DEATH: GLUCOCORTICOIDS AND SURVIVAL IN A WILD PRIMATE MODEL OF AGING Fernando Campos, University of Texas, San Antonio, San Antonio, Texas, United States
Chronic exposure to stressors has been linked with a wide range of detrimental effects on health in humans, laboratory animals, and a few wild animal populations.Glucocorticoids (GCs) mediate stress responses, and consequently GC levels are regularly measured in humans and other animals as biological markers of stress.However, no tests in humans or in natural populations of animals have yet established clear connections between environmental stressors, chronically elevated GCs, and shortened lifespan.To fill this gap, we used longitudinal data on wild female baboons to investigate the relationship between GC levels and survival-the single greatest determinant of variation in evolutionary fitness among female baboons.Using 14,173 GC measurements from 242 wild adult female baboons over 1634 female years, we document a powerful link between GCs and survival: females with relatively high current GCs or high lifelong cumulative GCs face an elevated risk of death.A hypothetical female who maintained GCs in the top 90% for her age across adulthood would be expected to lose 5.4 years of life relative to a female who maintained GCs in the bottom 10% for her age.Hence, differences among individuals in HPA axis activity provide valuable prognostic information about disparities in lifespan.Together, our results both support the value of GCs as a window into health, fitness, and aging and suggest that they may mechanistically contribute to the established link between sociality and lifespan.

FIVE BIODEMOGRAPHIC PRINCIPLES OF AGING THAT EMERGED FROM RESEARCH ON THE MEDITERRANEAN FRUIT FLY
James Carey, University of California, Davis, Davis, California, United States Because of its large size, visually-distinct sex differences, abundance in the wild and ease of rearing at both industrial and individual levels, the Mediterranean fruit fly (medfly) is an ideal model organism for conducting research on the demography of aging.I will present details on and implications for what I consider to be the five most interesting and important aging-related discoveries from the NIA-funded research my colleagues and I conducted over the past three decades using the medfly model.These discoveries include (1)Deceleration of mortality at advanced ages; (2) Equivocality of the gender gap due to context-specific sex mortality relationships; (3)Supine behavior as a biomarker of both morbidity onset and time-to-death; (4)A dietary disconnect between maximizing longevity vs maximizing lifetime reproduction; and (5)the life table population identity in which the fraction age x in a stationary population equals the fraction with x years to live.I will end with brief comments about the use of non-conventional model organisms for research on aging in both the laboratory and the field.

AGEISM EXPERIENCED AND EXPRESSED: MANIFESTATIONS ACROSS CONTEXTS AND TRANSGRESSORS Chair: Alison Chasteen
Ageism was first defined more than fifty years ago, yet its expressions and effects on society continue today.In this symposium, we examine manifestations of ageism across contexts and transgressors in order to determine the effects of ageism in light of a pandemic as well as a post-pandemic world.Important social contexts in which ageism plays a part are examined, such as the workplace and COVID-19 vaccination.As well, efforts to reduce ageism through confrontation are investigated, particularly with respect to reactions to ageist behavior.Providing a window into ageist communication during the pandemic, Bascu and colleagues detail how ageism was expressed in social media regarding policies for COVID-19 vaccination.Delving into the factors that drive older workers' decisions to remain or to leave an organization, both Lagacé et al and Swift investigate the role that perceived ageism plays.Lagacé and colleagues assess how older workers' perceptions of being the target of ageism impacts their well-being, their psychological disengagement, and their intentions to leave their organization.Swift considers how experiences of ageism in the workplace predict older workers' retirement intentions through reduced job satisfaction and lowered intrinsic motivation to work.Chasteen et al. test the impact of confronting ageism